Clinical and Demographic Factors Associated With COVID-19, Severe COVID-19, and SARS-CoV-2 Infection in Adults

Key Points Question What clinical and demographic factors are associated with rates of COVID-19, severe COVID-19, and SARS-CoV-2 infection? Findings In this secondary analysis of 57 692 participants randomized to the placebo groups of 4 COVID-19 vaccine phase 3 efficacy trials, exposure risks, demographics (age and race), and evidence of previous infection had the strongest associations with study outcomes. Meaning These findings could inform public health policy pertaining to prioritization for vaccination and risk mitigation efforts.


COVID-19
Severe COVID-19 Moderna PCR-confirmed SARS-CoV-2 infection AND one of the following: cough, shortness of breath or difficulty breathing, or clinical or radiological evidence of pneumonia; OR two of the following: fever (≥38° C), chills, myalgia, headache, sore throat, or new anosmia or ageusia.
Confirmed COVID-19 as per the Primary Efficacy Endpoint case definition, plus any of the following: clinical signs indicative of severe systemic illness (respiratory rate ≥ 30 per minute, heart rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FIO2 <300 mm Hg); respiratory failure or ARDS, (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation); evidence of shock (systolic blood pressure < 90 mmHg, diastolic BP < 60 mmHg or requiring vasopressors); significant acute renal, hepatic or neurologic dysfunction; admission to an ICU; or death.

AstraZeneca
PCR-confirmed SARS-CoV-2 infection AND one of the following: new or worsening dyspnea/shortness of breath, pneumonia diagnosed by chest X-ray or computed tomography scan, or oxygen saturation ≤ 94% on room air or requiring either new initiation or escalation in supplemental O2; OR two of the following: fever, new/worsening cough, myalgia, fatigue that interferes with activities of daily living, vomiting and/or diarrhea, or anosmia and/or ageusia.
SARS-CoV-2 RT-PCR-positive symptomatic illness plus any of the following: clinical signs at rest indicative of severe systemic illness (respiratory rate ≥ 30 breaths per minute, heart rate ≥ 125 beats per minute, oxygen saturation ≤ 93% on room air at sea level, or PaO2/FIO2 < 300 mm Hg); respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation); evidence of shock (systolic blood pressure < 90 mm Hg, diastolic blood pressure < 60 mm Hg, or requiring vasopressors); significant acute renal, hepatic, or neurologic dysfunction; admission to an ICU; or death. Janssen PCR or NAAT confirmation of SARS-CoV-2 infection AND ≥2 of the following symptoms (new or worsening): fever or chills, cough, heart rate ≥90 beats/minute, muscle or body pain, headache, new loss of taste or smell, sore throat, red or bruised-looking feet or toes, nausea, vomiting, or diarrhea; or one or more of the following signs or symptoms: shortness of breath, respiratory rate >20 breaths/minute, clinical or radiologic evidence of pneumonia, deep vein thrombosis, or abnormal oxygen saturation (but above 93%).
SARS-CoV-2 RT-PCR-positive symptomatic illness with any of the following: respiratory failure; evidence of shock (systolic blood pressure <90mm Hg, diastolic blood pressure <60 mm Hg, or requiring vasopressors); respiratory rate >30 breaths/minute; heart rate ≥125 beats/minute; oxygen saturation of 93% or less (ambient air at sea level), or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen <300 mm Hg; intensive care unit admission; significant acute renal, hepatic, or neurologic dysfunction; or death. eTable 2: Schedule of Anti-Nucleocapsid Protein Testing Across Protocols. Planned testing is shown through week 30 of the studies. Ranges are given for later timepoints to account for slight differences in the individual trials. Only data from samples accrued through the blinded, pre-crossover phases of the trials are included in this analysis. Participants were screened for symptomatic illness by passive surveillance and active surveillance at all study visits. In Moderna, routine non-symptom-driven SARS-CoV-2 PCR testing was performed at week 0, week 4, and at the Participant Decision Visit (this visit provided the opportunity for participants to be unblinded following Emergency Use Authorization (EUA) of COVID-19 vaccines). In Novavax, routine non-symptom-driven SARS-CoV-2 PCR testing was performed at week 0 and at the time of blinded crossover following EUA submission.